S-(2-pyridyl-1-oxide)-thioarylates



United States Patent 3,207,760 S-(Z-PYRIDYL-ll-l)XlDll)-THEQARYLATES Bernard B. Brown, Westfield, N .l assignor to S. B. Penick & Qompany, New York, N.Y., a corporation of Delaware No Drawing. Filed Apr. 10, 1962, Ser. No. 186,333 2 Claims. (Cl. Mil-2M3) This invention relates to certain novel pyridine-l-oxide derivatives. More particularly it relates to certain useful 2-thioarylates of pridine-l-oxide and a process for making these novel compounds.

This invention according to its compositional aspects includes the compounds of the formula:

where R is chosen from the group of substituted and unsubstituted aryl radicals. When R is a substituted aryl radical having the formula:

Y represents nuclear substituents on the aryl ring, each chosen from the group consisting of lower alkyl, lower alkoxy, halo and nitro radicals.

The term lower when used herein with respect to alkyl and alkoxy refers to such radicals having less than 5 carbon atoms.

where X may he chlorine or bromide and Y is as mentioned above.

The starting material for this process, 2-mercaptopyridine-l-oxide is described in U.S. Patent 2,686,786 issued August 17, 1954. Methods for the synthesis of this material are therein disclosed.

Among the acid-accepting reagents useful for promoting the reaction of the 2mercaptopyridine-l-oxide with the aroyl halides are pyridine, the picolines, dimethylaniline and the alkali metal and alkaline earth hydroxides. Any inert solvent, the organic acid-acceptors or mixtures of solvent and acceptors may serve as the reaction medium.

Alternately, an aqueous solution of the metal salts, preferably the alkali metal or alkaline earth salts of 2- mercaptopyridine-l-oxide can be directly reacted with acylating agent even in the absence of acid acceptors or organic solvents.

Among the substituted benzoyl and naphthoyl-acylating halides, the acid chlorides are the preferred halides. Among these, some that are useful for preparing the novel thioarylates of this reaction are benzoyl and naphthyol chlorides for preparing the nuclear unsubstituted compounds. The substituted compounds are prepared from such acid chlorides as 2-methyl-benzoyl chloride, 2,5- dichlorobenzoyl chloride, 3,5-dinitrobenzoyl chloride, 3- methoxybenzoyl chloride, 4 nitrobenzoyl chloride, 4- ethoxybenzoyl chloride, 3 isopropylbenzoyl chloride. Those acylating reactants are all known and many may be purchased. The synthesis of the others is routine by methods described in the literature.

Both reactants are used in equimolar quantities but a slight excess (10%) of the acylating agent is preferred. The reaction will proceed in good yield under simple laboratory conditions. Occasionally, these benzoyl halides, having alkyl substituents at both the 2 and 6 positions, especially those with longer alkyl chains, will not give good yields under simple conditions due to steric hindrance. To prepare substituted thiobenzoates of 2 pyridyl-l-oxides where the substituents are on the 2- and 6-positions it is preferred to react 2-chloropyridine-1- oxide with a metallic monothiobenzoate such as silver monothio-nuclear substituted-benzoates.

This type-reaction can be used to prepare all the other S-(Z-pyridyl-l-oxide) thioarylates of this invention, but the preparation of the metallic monothiobenzoate starting materials are cumbersome and expensive.

The compounds of this invention possess good antibacterial qualities. Against M. pyrogenes var. aureus and M. flavus #10240 ATCC, some of the novel compounds of this invention have the same order of activity on a weight basis as the antibiotics, Neomycin and Bacitra cin. In addition against Monolinia fructicola, (by the Spore Germination Test Tube Dilution Procedure) certain of the novel compounds of this invention demostrated an ED at concentrations of 0.25 part per million. When tested against tomato early blight in the greenhouse on growing plants, better than control was achievedwith 500 parts per million of S-(2-pyridyl-1- oxide)-3,5-dinitrothiobenzoate (Melting Point 133-134 centigrade), and 85% control with the same concentration of S-(2 pyridyl l-oxide)-2,5-dichlorothiobenzoate (Melting Point l35-136.5 centigrade). The blight control was achieved without signs of phytotoxicity or alteration in either the growth pattern or fruit quality. This is in contrast with the known aralkyl thioesters of 2-pyridyl-1-oxide which are phytotoxic (cf. US. Patent 2,922,792 where they are disclosed as herbicides).

This invention will be illustrated by the following examples which, while showing preferred modes of preparing representative compounds within the "broad ambit of this invention, are not to be construed as limiting. Appropriate changes in reaction conditions and recovery procedures may be made in the manner normally employed by those possessing the usual skill of this art. By appropriate changes in the starting materials the other compounds within the scope of this invention may also be prepared.

EXAMPLE ONE chloride. The residue is then recrystallized from acetone to yield I the S-('2-pyridyl1-oxide)-thiobe,nzoate.

ture and agitation for about 2 hours. Cool and filter the reaction mixture and wash the precipitate with cold benzene. Slurry the precipitate in a cold solution of 3% sodium bicarbonate in water to remove the excess benzoyl Filter the residue and wash it with cold water.

EXAMPLE TWO S-(Z-pyridyl-l oxide)-3,5-dinitrothio benzoote N03 ml i N *Q J, N02

Following the procedure of Example One but substitute .3,5-dirlitro benzoyl chloride for the benzoyl chloride of that example to obtain S-(Z-pyridyld-oxide)-3,S-dinitrothiobenzoate.

EXAMPLE THREE S- 2-pyria'yl-1 oxide) -2,5-dichl0rothiobenzoate Cl 0 I S t \N t 0 01 Following the procedure of Example One but substitute 2,5-diohlorobenzoyl chloride for the benzoyl chloride of that example to obtain S(2-pyridyl 1-oxide)-2,S-dichlorothiobenzoate. EXAMPLE FOUR S-(Z-pyridyl-I oxide) -3,4-dime'tlzylthiobenzoate Following the procedure of Example One but substitute 3,4-dimethylbenzoyl chloride for the benzoyl chloride of that example to obtain S-(Z-pyridyl-l-oxide)-3,4-dimethylthiobenzo'ate.

EXAMPLE IFIVE S- (2-pyridyl-1oxide) -3 nitr0-4 ehlorothiobenzoate Following the procedure of Example One but substitute 3-nituo-4-chlorobenzoyl chloride for the benzoyl chloride of that example to obtain S-(2-py ridyl-1-oxide)3-nitro 4 chlorothiobenzoate.

EXAMPLE SIX S-(Z-pyridyl-l oxide) -thi0naphth01ate Following the procedure of Example One but substitute l-naphthol chloride for the chloride of that example to obtain S- (2-pyridyl1-oxide) -thion-aphtl1oa-te.

Cil

EXAMPLE SEVEN S (2-pyridyl-1 oxide) -3methy lthiobenzoate Following the procedure of Example One but substitute 3-methylbenzoyl chloride for the benzoyl chloride of that example to obtain S-(2-py-ridyl-1-oxide)3-methylthiobenzoate.

EXAMPLE EIGHT S- (Z-pyridyl-I oxide) -3-m ethoxythz'obenzoate OCH} r i I Follow the procedure of Example One but substitute S-methoxybenzoyl chloride for the benzoyl chloride of that example to obtain S-(Z-pyridyl-l-oxide)-3-methoxythiobenzoate.

EXAMPLE NINE S -(2-pyridyl-1 oxide -4-isopr0pylthi0ben20ate EXAMPLE TEN S- (Z-pyridyl-l oxide -2-chl0r0thi0benz0ate Follow the procedure of Example One but substitute 2-chlorobenzoyl chloride for the benzoyl chloride of that example to obtain S-(2-pyridyl-1-oxide)-2-chlorothiobenzoate.

EXAMPLE ELEVEN S-(Z-pyridyl-l oxide -3-nitr0thi0benz0ate -L l 0 NO:

Follow the procedure of Example One but substitute 3-nitrobenzoyl chloride for the benzoyl chloride of that example to obtain S-(2-pyridyl-l-oXide)-3-nitrothiobenzoate.

EXAMPLE TWELVE S- (Z-pyridyl-I oxide 3,5-dinitr0thi0benz0ate While cooling with an ice-bath, slowly add 0.11 mole of 3,5-dinitrobenzoyl chloride to an aqueous solution of sodio-2-mercaptopyridine 1 oxide. Maintain vigorous agitation during the addition. When the addition is completed, remove the ice-bath and continue the stirring for at least an hour. Filter the precipitate and Wash it With cold Water. Slurry the precipitate in saturated sodium bicarbonate solution to remove the excess of the benzoyl chloride. Refilter the precipitate and Wash to remove the bicarbonate. Recrystallize the precipitate from aqueous acetone or aqueous alcohol to recover S-(2-pyridy1-1- oxide)-3,5-dinitrothiobenzoate.

I claim:

1. S-(2-pyridyl-1-oxide)-3,S-dinitrothiobenzoate.

2. S- Z-pyridyll-oxide -3nitro-chlorothiobenzoate.

References Cited by the Examiner UNITED STATES PATENTS 2,686,786 8/54 Shaw et a1 260-294.8 2,742,393 4/56 Bernstein et al. 260294.8 2,742,476 4/56 Bernstein et al. 260294.8

6 2,786,847 3/57 Cislak 260294.8 2,809,971 10/57 Bernstein et a1 260-294.8 2,922,790 1/60 Rock-ett et al. 260294.8 2,922,791 1/ 60 Rockett 260-2948 2,922,792 1/ 60 Rockett 260-294.8 2,922,793 1/ 60 Rockett 260-2948 2,932,647 4/ 60 Rockett 260-294.8 2,940,978 6/60 Brown 260-2948 OTHER REFERENCES Bernthsen and Sudborough: Textbook of Organic Chemistry, 1931 edition, pages 37281 (Van Nostrand).

Kharasch: Organic Sulfur Compounds, volume 1, page 422 (1961) (Pergamon Press).

15 WALTER A. MODANCE, Primary Examiner.

IRVING MARCUS, Examiner.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3,207,760 September 21, 1965 Bernard B. Brown It is hereby certified that error appears in the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.

Column 5, line 11, for 3-ni'tro chlorothiobenzoate" read 3nitro-4chlorothiobenzoate I Signed and sealed this 10th day of January 1967 (SEAL) Attest:

ERNEST W. SWIDER Attesting Officer EDWARD J. BRENNER Commissioner of Patents 

1. S-(2-PYRIDYL-1-OXIDE)-3,5-DINITHROTHIOBENZOATE. 